硬脂酰辅酶A去饱和酶1在结肠癌细胞5-氟尿嘧啶耐药中的作用

周洪旭; 董严; 李建军

doi:10.16016/j.1000-5404.202009227

您当前的位置：

首页 >

文章列表页 >

硬脂酰辅酶A去饱和酶1在结肠癌细胞5-氟尿嘧啶耐药中的作用

基础医学 | 更新时间：2026-01-09

- 硬脂酰辅酶A去饱和酶1在结肠癌细胞5-氟尿嘧啶耐药中的作用
- Role of stearoyl CoA desaturase 1 in resistance of colon cancer cells to 5-fluorouracil
- 第三军医大学学报 2021年43卷第5期页码：395-402
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家自然科学基金青年科学基金(81803028)
- DOI：10.16016/j.1000-5404.202009227
  中图分类号：
- 收稿：2020-09-26，
  
  纸质出版：2021-03-15
- 稿件说明：
移动端阅览
周洪旭, 董严, 李建军. 硬脂酰辅酶A去饱和酶1在结肠癌细胞5-氟尿嘧啶耐药中的作用[J]. 第三军医大学学报, 2021,43(5):395-402.

Hongxu ZHOU, Yan DONG, Jianjun LI. Role of stearoyl CoA desaturase 1 in resistance of colon cancer cells to 5-fluorouracil[J]. Journal of Third Military Medical University, 2021, 43(5): 395-402.
周洪旭, 董严, 李建军. 硬脂酰辅酶A去饱和酶1在结肠癌细胞5-氟尿嘧啶耐药中的作用[J]. 第三军医大学学报, 2021,43(5):395-402. DOI： 10.16016/j.1000-5404.202009227.

Hongxu ZHOU, Yan DONG, Jianjun LI. Role of stearoyl CoA desaturase 1 in resistance of colon cancer cells to 5-fluorouracil[J]. Journal of Third Military Medical University, 2021, 43(5): 395-402. DOI： 10.16016/j.1000-5404.202009227.

摘要

Abstract

Objective

To construct a 5-fluorouracil (5-FU)-resistant colon cancer cell line

and to investigate the role of stearoyl CoA desaturase 1 (SCD1) in the resistance of colon cancer cells to 5-FU.

Methods

Drug resistance to 5-FU was induced in colon cancer cell line HCT116 by increasing the concentration intermittently and repeated inducing and screening with high concentration to produce drug-resistant cell line HCT116/5FU. The survival rates and half maximal inhibitory concentration (IC

) were measured by CCK-8 assay in HCT116

HCT116/5FU

HCT116-Control and HCT116-OE-SCD1 cells after the treatment of 5-FU. Immunohistochemical assay was employed to measure the expression of SCD1 after the fabrication of colon cancer and paracancerous tissue chips. Quantitative PCR and Western blotting were applied to detect the expression of SCD1. CCK-8 assay

plate clone formation and crystal violet staining were used to detect cell survival status. The apoptotic rates were detected by AnnexinV-FITC/PI double staining. HCT116-Control and HCT116-OE-SCD1 subcutaneous xenograft models in nude mice were established to observe the effect of SCD1 on tumor growth. Western blotting was carried out to detect the expression of apoptosis-related proteins.

Results

The IC

value of 5-FU was 0.90±0.06 μg/mL in HCT116 cells

and 15.02±0.81 μg/mL in HCT116/5FU cells

with a multiple of resistance about 16.7 ti

mes. The expression of SCD1 was higher in drug resistant colon cancer tissues than in common colon cancer tissues and corresponding paracancerous tissues. And its expression level was also higher in HCT116/5FU cells than HCT116 cells. Overexpression of SCD1 reduced the apoptotic rate of colon cancer cells(

0.01). Xenograft nude mouse model indicated that SCD1 overexpression enhanced the resistance of colon cancer cells to 5-FU. After 48 h of 5-FU treatment

the expression of bcl-2 and caspase3 were lower in HCT116-OE-SCD1 group than HCT116-Control group(

0.01).

Conclusion

The 5-FU-resistant model of colon cancer HCT116/5FU cells is successfully established. SCD1 promotes the resistance to 5-FU in colon cancer cells.

关键词

Keywords

references

SIEGEL R L MILLER K D GODING SAUER A Colorectal cancer statistics, 2020 CA A Cancer J Clin 2020 70 3 145 164 10.3322/caac.21601 SIEGEL R L, MILLER K D, GODING SAUER A, et al . Colorectal cancer statistics, 2020[J ] . CA A Cancer J Clin, 2020, 70(3): 145-1 64. DOI:10.3322/caac.21601.

WANQING C KEXIN S RONGSHOU Z Cancer incidence and mortality in China, 2014 Chin J Cancer Res 2018 30 1 1 12 WANQING C, KEXIN S, RONGSHOU Z, et al . Cancer incidence and mortality in China, 2014[J ] . Chin J Cancer Res, 2018, 30(1): 1-12.

KOZOVSKA Z GABRISOVA V KUCEROVA L Colon cancer: cancer stem cells markers, drug resistance and treatment Biomed Pharmacother 2014 68 8 911 916 10.1016/j.biopha.2014.10.019 KOZOVSKA Z, GABRISOVA V, KUCEROVA L. Colon cancer: cancer stem cells markers, drug resistance and treatment[J]. Biomed Pharmacother, 2014, 68(8): 911-916. DOI:10.1016/j.biopha.2014.10.019.

SU P YANG Y WANG G Curcumin attenuates resistance to irinotecan via induction of apoptosis of cancer stem cells in chemoresistant colon cancer cells Int J Oncol 2018 53 3 1343 1353 10.3892/ijo.2018.4461 SU P, YANG Y, WANG G, et al . Curcumin attenuates resistance to irinotecan via induction of apoptosis of cancer stem cells in chemoresistant colon cancer cells[J ] . Int J Oncol, 2018, 53(3): 1343-1353. DOI:10.3892/ijo.2018.4461.

LIN G L TING H J TSENG T C Modulation of the mRNA-binding protein HuR as a novel reversal mechanism of epirubicin-triggered multidrug resistance in colorectal cancer cells PLoS ONE 2017 12 10 e0185625 10.1371/journal.pone.0185625 LIN G L, TING H J, TSENG T C, et al . Modulation of the mRNA-binding protein HuR as a novel reversal mechanism of epirubicin-triggered multidrug resistance in colorectal cancer cells[J ] . PLoS ONE, 2017, 12(10): e0185625. DOI:10.1371/journal.pone.0185625.

VASAN N BASELGA J HYMAN D M A view on drug resistance in cancer Nature 2019 575 7782 299 309 10.1038/s41586-019-1730-1 VASAN N, BASELGA J, HYMAN D M. A view on drug resistance in cancer[J]. Nature, 2019, 575(7782): 299-309. DOI:10.1038/s41586-019-1730-1.

PRESLER M WOJTCZYK-MIASKOWSKA A SCHLICHTHO-LZ B Increased expression of the gene encoding stearoyl-CoA desaturase 1 in human bladder cancer Mol Cell Biochem 2018 447 1/2 217 224 10.1007/s11010-018-3306-z PRESLER M, WOJTCZYK-MIASKOWSKA A, SCHLICHTHO-LZ B, et al . Increased expression of the gene encoding stearoyl-CoA desaturase 1 in human bladder cancer[J ] . Mol Cell Biochem, 2018, 447(1/2): 217-224. DOI:10.1007/s11010-018-3306-z.

ANGELUCCI C D'ALESSIO A IACOPINO F Pivotal role of human stearoyl-CoA desaturases (SCD1 and 5) in breast cancer progression: oleic acid-based effect of SCD1 on cell migration and a novel pro-cell survival role for SCD5 Oncotarget 2018 9 36 24364 24380 10.18632/oncotarget.25273 ANGELUCCI C, D'ALESSIO A, IACOPINO F, et al . Pivotal role of human stearoyl-CoA desaturases (SCD1 and 5) in breast cancer progression: oleic acid-based effect of SCD1 on cell migration and a novel pro-cell survival role for SCD5[J ] . Oncotarget, 2018, 9(36): 24364-24380. DOI:10.18632/oncotarget.25273.

RAN H ZHU Y DENG R Stearoyl-CoA desaturase-1 promotes colorectal cancer metastasis in response to glucose by suppressing PTEN J Exp Clin Cancer Res 2018 37 1 54 10.1186/s13046-018-0711-9 RAN H, ZHU Y, DENG R, et al . Stearoyl-CoA desaturase-1 promotes colorectal cancer metastasis in response to glucose by suppressing PTEN[J ] . J Exp Clin Cancer Res, 2018, 37(1): 54. DOI:10.1186/s13046-018-0711-9.

COLACINO J A MCDERMOTT S P SARTOR M A Transcriptomic profiling of curcumin-treated human breast stem cells identifies a role for stearoyl-coa desaturase in breast cancer prevention Breast Cancer Res Treat 2016 158 1 29 41 10.1007/s10549-016-3854-4 COLACINO J A, MCDERMOTT S P, SARTOR M A, et al . Transcriptomic profiling of curcumin-treated human breast stem cells identifies a role for stearoyl-coa desaturase in breast cancer prevention[J ] . Breast Cancer Res Treat, 2016, 158(1): 29-41. DOI:10.1007/s10549-016-3854-4.

NOTO A DE VITIS C PISANU M E Stearoyl-CoA-desaturase 1 regulates lung cancer stemness via stabilization and nuclear localization of YAP/TAZ Oncogene 2017 36 32 4573 4584 10.1038/onc.2017.75 NOTO A, DE VITIS C, PISANU M E, et al . Stearoyl-CoA-desaturase 1 regulates lung cancer stemness via stabilization and nuclear localization of YAP/TAZ[J ] . Oncogene, 2017, 36(32): 4573-4584. DOI:10.1038/onc.2017.75.

IGAL R A Stearoyl CoA desaturase-1: New insights into a central regulator of cancer metabolism Biochim Biophys Acta 2016 1861 12 pt a 1865 1880 10.1016/j.bbalip.2016.09.009 IGAL R A. Stearoyl CoA desaturase-1: New insights into a central regulator of cancer metabolism[J]. Biochim Biophys Acta, 2016, 1861(12 pt a): 1865-1880. DOI:10.1016/j.bbalip.2016.09.009.

CHEN L REN J YANG L Stearoyl-CoA desaturase-1 mediated cell apoptosis in colorectal cancer by promoting ceramide synthesis Sci Rep 2016 6 19665 10.1038/srep19665 CHEN L, REN J, YANG L, et al . Stearoyl-CoA desaturase-1 mediated cell apoptosis in colorectal cancer by promoting ceramide synthesis[J ] . Sci Rep, 2016, 6: 19665. DOI:10.1038/srep19665.

WANG L ZHANG L LI L Small-molecule inhibitor targeting the Hsp90-Cdc37 protein-protein interaction in colorectal cancer Sci Adv 2019 5 9 eaax2277 10.1126/sciadv.aax2277 WANG L, ZHANG L, LI L, et al . Small-molecule inhibitor targeting the Hsp90-Cdc37 protein-protein interaction in colorectal cancer[J ] . Sci Adv, 2019, 5(9): eaax2277. DOI:10.1126/sciadv.aax2277.

OU J J PENG Y YANG W W ABHD5 blunts the sensitivity of colorectal cancer to fluorouracil via promoting autophagic uracil yield Nat Commun 2019 10 1078 10.1038/s41467-019-08902-x OU J J, PENG Y, YANG W W, et al . ABHD5 blunts the sensitivity of colorectal cancer to fluorouracil via promoting autophagic uracil yield[J ] . Nat Commun, 2019, 10: 1078. DOI:10.1038/s41467-019-08902-x.

WEBBER E M KAUFFMAN T L O'CONNOR E Systematic review of the predictive effect of MSI status in colorectal cancer patients undergoing 5FU-based chemotherapy BMC Cancer 2015 15 156 10.1186/s12885-015-1093-4 WEBBER E M, KAUFFMAN T L, O'CONNOR E, et al . Systematic review of the predictive effect of MSI status in colorectal cancer patients undergoing 5FU-based chemotherapy[J ] . BMC Cancer, 2015, 15: 156. DOI:10.1186/s12885-015-1093-4.

DE ANGELIS P M SVENDSRUD D H KRAVIK K L Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery Mol Cancer 2006 5 1 1 25 10.1186/1476-4598-5-20 DE ANGELIS P M, SVENDSRUD D H, KRAVIK K L, et al . Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery[J ] . Mol Cancer, 2006, 5(1): 1-25. DOI:10.1186/1476-4598-5-20.

CHE J PAN L YANG X Thymidine phosphorylase expression and prognosis in colorectal cancer treated with 5-fluorouracil-based chemotherapy: a meta-analysis Mol Clin Oncol 2017 7 6 943 952 10.3892/mco.2017.1436 CHE J, PAN L, YANG X, et al . Thymidine phosphorylase expression and prognosis in colorectal cancer treated with 5-fluorouracil-based chemotherapy: a meta-analysis[J ] . Mol Clin Oncol, 2017, 7(6): 943-952. DOI:10.3892/mco.2017.1436.

KUGIMIYA N NISHIMOTO A HOSOYAMA T JAB1-STAT3 activation loop is associated with recurrence following 5-fluorouracil-based adjuvant chemotherapy in human colorectal cancer Oncol Lett 2017 14 5 6203 6209 10.3892/ol.2017.6994 KUGIMIYA N, NISHIMOTO A, HOSOYAMA T, et al . JAB1-STAT3 activation loop is associated with recurrence following 5-fluorouracil-based adjuvant chemotherapy in human colorectal cancer[J ] . Oncol Lett, 2017, 14(5): 6203-6209. DOI:10.3892/ol.2017.6994.

HOLOHAN C VAN SCHAEYBROECK S LONGLEY D B Cancer drug resistance: an evolving paradigm Nat Rev Cancer 2013 13 10 714 726 10.1038/nrc3599 HO LOHAN C, VAN SCHAEYBROECK S, LONGLEY D B, et al . Cancer drug resistance: an evolving paradigm[J ] . Nat Rev Cancer, 2013, 13(10): 714-726. DOI:10.1038/nrc3599.

GUO C MA J L DENG G L ZEB1 promotes oxaliplatin resistance through the induction of epithelial-mesenchymal transition in colon cancer cells J Cancer 2017 8 17 3555 3566 10.7150/jca.20952 GUO C, MA J L, DENG G L, et al . ZEB1 promotes oxaliplatin resistance through the induction of epithelial-mesenchymal transition in colon cancer cells[J ] . J Cancer, 2017, 8(17): 3555-3566. DOI:10.7150/jca.20952.

GARG M Epithelial plasticity and cancer stem cells: Major mechanisms of cancer pathogenesis and therapy resistance World J Stem Cells 2017 9 8 118 126 10.4252/wjsc.v9.i8.118 GARG M. Epithelial plasticity and cancer stem cells: Major mechanisms of cancer pathogenesis and therapy resistance[J]. World J Stem Cells, 2017, 9(8): 118-126. DOI:10.4252/wjsc.v9.i8.118.

HUANG G M JIANG Q H CAI C SCD1 negatively regulates autophagy-induced cell death in human hepatocellular carcinoma through inactivation of the AMPK signaling pathway Cancer Lett 2015 358 2 180 190 10.1016/j.canlet.2014.12.036 HUANG G M, JIANG Q H, CAI C, et al . SCD1 negatively regulates autophagy-induced cell death in human hepatocellular carcinoma through inactivation of the AMPK signaling pathway[J ] . Cancer Lett, 2015, 358(2): 180-190. DOI:10.1016/j.canlet.2014.12.036.

SOUTHAM A D KHANIM F L HAYDEN R E Drug redeployment to kill leukemia and lymphoma cells by disrupting SCD1-mediated synthesis of monounsaturated fatty acids Cancer Res 2015 75 12 2530 2540 10.1158/0008-5472.can-15-0202 SOUTHAM A D, KHANIM F L, HAYDEN R E, et al . Drug redeployment to kill leukemia and lymphoma cells by disrupting SCD1-mediated synthesis of monounsaturated fatty acids[J ] . Cancer Res, 2015, 75(12): 2530-2540. DOI:10.1158/0008-5472.can-15-0202 .

CARBONE M MELINO G Stearoyl CoA desaturase regulates ferroptosis in ovarian cancer offering new therapeutic perspectives Cancer Res 2019 79 20 5149 5150 10.1158/0008-5472.can-19-2453 CARBONE M, MELINO G. Stearoyl CoA desaturase regulates ferroptosis in ovarian cancer offering new therapeutic perspectives[J]. Cancer Res, 2019, 79(20): 5149-5150. DOI:10.1158/0008-5472.can-19-2453.

XIE H TANG C H SONG J H IRE1α RNase-dependent lipid homeostasis promotes survival in Myc-transformed cancers J Clin Invest 2018 128 4 1300 1316 10.1172/jci95864 XIE H, TANG C H, SONG J H, et al . IRE1α RNase-dependent lipid homeostasis promotes survival in Myc-transformed cancers[J ] . J Clin Invest, 2018, 128(4): 1300-1316. DOI:10.1172/jci95864.

DANIAL N N KORSMEYER S J Cell death: critical control points Cell 2004 116 2 205 219 10.1016/s0092-8674(04)00046-7 DANIAL N N, KORSMEYER S J. Cell death: critical control points[J]. Cell, 2004, 116(2): 205-219. DOI:10.1016/s0092-8674(04)00046-7.

DENISENKO T V SOROKINA I V GOGVADZE V Mitotic catastrophe and cancer drug resistance: a link that must to be broken Drug Resist Updat 2016 24 1 12 10.1016/j.drup.2015.11.002 DENISENKO T V, SOROKINA I V, GOGVADZE V, et al . Mitotic catastrophe and cancer drug resistance: a link that must to be broken[J ] . Drug Resist Updat, 2016, 24: 1-12. DOI:10.1016/j.drup.2015.11.002.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

结肠癌HT29多细胞球的培养及其结构与生物学特性的观察

缺氧诱导因子-1α纳米抑制剂的构建及在逆转结直肠癌细胞化疗耐药中的应用

沉默高迁移率族蛋白B1对胶质母细胞瘤细胞恶性生物学行为的抑制

miRNA-200b逆转肝细胞癌HepG2细胞对索拉菲尼的耐药性及其相关机制

下调miR-4443/TIMP2信号通路增强HepG2细胞对索拉非尼的敏感性